CADHERINS IN ORAL SQUAMOUS CELL CARCINOMAS

描述(改编自《调查员摘要》)：长期目标 这个项目的重点是了解细胞与细胞之间的相互作用 在浸润性癌中表达下调。需要检验的假设是 在一些肿瘤中出现了一种新的E-钙粘蛋白失活机制，因此 促进细胞间相互作用的丧失。现建议将 不适当的钙粘附素(即，上皮细胞中的间质钙粘附素 细胞)下调正常的内源性上皮钙粘附素(S)。 已经获得的初步数据表明，不适当的表达 鳞状上皮细胞对N-钙粘附素的作用均下调E-钙粘附素 并导致细胞-细胞黏附减少和更分散， 成纤维细胞样形态。具体目标是：1)确定 N-钙粘附素的结构域(S)负责下调表达 E-钙粘附素在口腔鳞状细胞中的表达及其与成纤维细胞表型的关系 2)确定N-钙粘附素在其 通过决定改变鳞状上皮细胞表型的能力 如果其他非上皮细胞钙粘附素(例如，钙粘附素4、钙粘附素6或 钙粘附素11)产生类似的结果；以及3)确定机制 这赋予鳞状上皮细胞一种分散的表型。这个 表型的改变可能是由于许多活动引起的，包括减少 细胞间黏附或运动性增加。来帮助理清这两个问题 可能，将进行研究下调E-钙粘附素 表达，而不存在改变表达的复杂情况 N-钙粘附素。

DESCRIPTION (Adapted from investigator's Abstract): The long-term objective of this project is to understand how cell-cell interactions are down-regulated in invasive carcinomas. The hypothesis to be tested is that a novel mechanism of E-cadherin inactivation occurs in some tumors, thus promoting loss of cell-cell interactions. It is proposed that expression of an inappropriate cadherin (i.e., a mesenchymal cadherin in an epithelial cell) down-regulates the normal endogenous epithelial cadherin(s). Preliminary data have been obtained suggesting that inappropriate expression of N-cadherin by squamous epithelial cells both down-regulates E-cadherin and results in decreased cell-cell adhesion and a more scattered, fibroblast-like morphology. The specific aims are: 1) To determine which domain(s) of N-cadherin are responsible for down-regulating the expression of E-cadherin and for producing a fibroblastic phenotype in oral squamous epithelial cells; 2) To determine whether N-cadherin is unique in its ability to alter the phenotype of squamous epithelial cells by determining if other non-epithelial cell cadherins (e.g., cadherin 4, cadherin 6 or cadherin 11) produce similar results; and 3) To determine the mechanisms that confer a scattered phenotype upon squamous epithelial cells. The change in phenotype may be due to a number of activities including decreased cell-cell adhesion or increased motility. To help sort out these two possibilities, studies will be performed to down-regulate E-cadherin expression without the complications of altering the expression of N-cadherin.